Gene targeting using zinc finger nucleases
Abstract
The ability to achieve site-specific manipulation of the mammalian genome has widespread implications for basic and applied research. Gene targeting is a process in which a DNA molecule introduced into a cell replaces the corresponding chromosomal segment by homologous recombination, and thus presents a precise way to manipulate the genome. In the past, the application of gene targeting to mammalian cells has been limited by its low efficiency. Zinc finger nucleases (ZFNs) show promise in improving the efficiency of gene targeting by introducing DNA double-strand breaks in target genes, which then stimulate the cell's endogenous homologous recombination machinery. Recent results have shown that ZFNs can be used to create targeting frequencies of up to 20% in a human disease-causing gene. Future work will be needed to translate these in vitro findings to in vivo applications and to determine whether zinc finger nucleases create undesired genomic instability.
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Different endonucleases employed as second generation tools include zinc finger nucleases (ZFN), meganucleases, TALEN, and CRISPR/Cas9.
“As second generation tools, different endonucleases have been employed.This category includes zinc finger nucleases (ZFN), meganucleases, transcription activators like effectors nucleases (TALEN) and CRISPR/Cas9 (Durai et al., 2005;Porteus and Carroll 2005;Cabaniols et al., 2010;Silva et al., 2011;Kim et al., 2012;Sanjana et al., 2012;Cho et al., 2013;Sun and Zhao, 2013).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Porteus and Carroll 2005
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Self-citation
- Authors
- Porteus, M. H., & Carroll, D.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- University of Utah (US)
- Corresponding author
- Porteus, Matthew H
- Venue
- Nature Biotechnology
- Published
- 2005-08
- Volume
- 23
- Issue
- 8
- Pages
- 967-973
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2004360848
- Cited by
- 641
- References
- 2
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 29 · 2023: 15 · 2022: 22 · 2021: 23 · 2020: 23 · 2019: 22 · 2018: 29 · 2017: 37 · 2016: 33 · 2015: 34 · 2014: 32 · 2013: 46 · 2012: 50
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- zinc finger nucleases, gene targeting, homologous recombination, DNA double-strand breaks, targeting efficiency, genomic instability
- MeSH terms
- Deoxyribonucleases, DNA, DNA Damage, DNA Repair, Genetic Engineering, Recombination, Genetic, Zinc Fingers, Gene Targeting
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